Systems that involve the detection of light are used in a variety of contexts. For example, systems that involve the detection and analysis of light are used in performing optical spectroscopic assays, including luminescence and absorption assays. These assays may be used to characterize the components and properties of molecular systems, and recently have been used in high-throughput screening procedures to identify candidate drug compounds.
High measurement throughput and high measurement precision are two valuable characteristics of light detection systems, particularly for drug discovery. Throughput and precision largely depend on the architecture and design of the detection system. However, the end-user can fine-tune the throughput and precision on some detection systems by adjusting instrument settings. Of these tunable settings, the most significant is detection time. In detection modes that use continuous light sources and in chemiluminescence modes, the detection time may be determined by setting an “integration” time. In detection modes that use a flash lamp, the detection time may be determined by the number of times the lamp flashes.
Throughput typically is increased by decreasing the detection time. However, many photoluminescence and chemiluminescence assays are shot-noise limited, so that decreasing the detection time results in lower detection precision. In cases such as these, where the time and precision are inversely related (i.e., where longer measurements generally correspond to more precise measurements), the end-user endeavors to strike a balance between detection throughput and detection precision. This balance often is achieved by trial-and-error: the end-user prepares test samples, and then reads the samples repeatedly in the detection system to empirically optimize the trade-off between throughput and precision.
The above process can be time consuming and tedious for the user, even for simple assays in which every sample has a similar photoluminescence or chemiluminescence intensity. However, in many assays, intensities vary from sample to sample. These assays are particularly troublesome to optimize. If the user sets a large detection time, such that adequate precision is achieved for low-intensity samples, then high-intensity samples will be “over-detected,” with a decrease in overall throughput. Likewise, if the user sets a small detection time, to achieve adequate precision for high-intensity samples, then low-intensity samples will be detected with poor precision. Ultimately, the end-user must compromise either throughput or precision or both.
Light-detection systems may suffer from additional shortcomings. For example, such systems may be limited in range, so that they accurately detect light only within some relatively narrow range of intensities. Such systems also may require user intervention to alter the detection range, if the range may be altered at all. Such systems also may be limited to either discrete or analog detection, so that either they discretely count individual quanta or photons of light, or they integrate an analog value corresponding to such quanta, but they do not do both. Such systems also may require significant periods of time to make measurements. These shortcomings may be found singly or in combination, and these shortcomings may be particularly significant in the context of high-throughput screening, where it may be necessary to perform tens or hundreds of thousands of measurements per day.